title: omega-Fluoromethyl analogues of omega-amino acids as irreversible inhibitors of 4-aminobutyrate:2-oxoglutarate aminotransferase.
abstract: omega-Monofluoromethyl and omega-difluoromethyl analogues of the known substrates of GABA-T, beta-alanine, gamma-aminobutyric acid, and 5-aminopentanoic acid, are time-dependent inhibitors of purified 4-aminobutyrate: 2-oxoglutarate aminotransferase (GABA-T). The inhibitory activity decreases with increasing chain length. In vitro, inhibitory activity decreases with increasing fluorine substitution of the methyl group. In vivo, beta-difluoromethyl-beta-alanine and 2,4-difluoro-3-aminobutyric acid are the most potent GABA-T inhibitors ever reported. Trifluoromethyl derivatives are devoid of GABA-T inhibitory activity in vitro or in vivo.
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D007700:Kinetics; D051379:Mice; D013329:Structure-Activity Relationship; D000637:Transaminases / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid; D000637:Transaminases; D000612:4-Aminobutyrate Transaminase